Abstract/Summary Prostate cancer is the most frequently diagnosed cancer in US men (except for non-melanomatous skin cancer). Many patients with prostate cancer will undergo years of androgen deprivation therapy (ADT). A multitude of side effects and risks of ADT have been described in the past and include a range of constitutional symptoms, loss of libido and impotence. However, the impact of ADT on cognitive functions, a major determinant of quality of life, remains unclear. Changes in cognitive performance have been reported but results of previous studies using neuropsychological tests alone have been equivocal. We hypothesize that ADT leads to impaired cognitive function that are not sufficiently recognized by neuropsychological testing as many of these test were developed to detect relatively severe cognitive decline, such as in Alzheimer's Dementia or after traumatic brain injury. This pilot study proposes to use functional brain imaging in combination with a behavioral task that examines critical frontal executive function to evaluate the effects of ADT on cognition. The results of functional brain imaging before and after initiation of ADT in prostate cancer patients without overt metastatic disease will be correlated to results of traditional neurocognitive tests and quality-of-life questionnaires. Age-matched subjects with prostate cancer who have never been treated with ADT will be enrolled to the control arm. The proposed study aims to obtain critical data in preparation for larger scale studies that further examine the effects of hormonal treatments on cognition and their potential preventability or reversibility. Understanding the neural basis of potential cognitive impairment as a result of ADT can help to identify individuals at highest risk and lead to new strategies to minimize cognitive changes related to ADT. This would result in improved quality of care for future prostate cancer patients. Furthermore, results of this study could underscore the utility of functional magnetic brain imaging to assess the impact on cognition of other pharmacological cancer treatments. PUBLIC HEALTH RELEVANCE: Narrative Many men with prostate cancer will be affected by side effects of hormonal therapy. The impact of hormonal therapy for prostate cancer on cognitive function, a major determinant of quality of life, remains unclear. This study proposes to use brain imaging to directly measure the effects of hormonal therapy on cognition in patients with prostate cancer before and after initiation of hormonal therapy. [The results of brain imaging will be correlated with scores obtained by neurocognitive testing and quality-of-life-questionnaires.]